CN106588887A - Compound as well as preparation method thereof and applications - Google Patents

Compound as well as preparation method thereof and applications Download PDF

Info

Publication number
CN106588887A
CN106588887A CN201510672520.1A CN201510672520A CN106588887A CN 106588887 A CN106588887 A CN 106588887A CN 201510672520 A CN201510672520 A CN 201510672520A CN 106588887 A CN106588887 A CN 106588887A
Authority
CN
China
Prior art keywords
compound
dmso
nmr
ppm
methyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201510672520.1A
Other languages
Chinese (zh)
Other versions
CN106588887B (en
Inventor
贺红武
何海峰
冯玲玲
彭浩
谭效松
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huazhong Normal University
Original Assignee
Huazhong Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Huazhong Normal University filed Critical Huazhong Normal University
Priority to CN201510672520.1A priority Critical patent/CN106588887B/en
Publication of CN106588887A publication Critical patent/CN106588887A/en
Application granted granted Critical
Publication of CN106588887B publication Critical patent/CN106588887B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Dentistry (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Agronomy & Crop Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention provides a compound as well as a preparation method thereof and applications, especially the compound shown in a formula I or enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, crystalline hydrates, ketone-enol tautomeric compounds or solvates thereof, wherein R1 is hydrogen or iodine, and X is O, S or NH; Y is carbonyl, sulfonyl or optionally substituted aromatic heterocyclic group; Z is methyl, optionally substituted aromatic heterocyclic group, optionally substituted alkyl or optionally substituted phenyl; n is 1, 2 and 3. The compound can be applied to treatment or prevention of plant diseases and removing of blue algae.

Description

Compound and preparation method and application thereof
Technical Field
The invention relates to the field of chemistry, in particular to a compound and a preparation method and application thereof, and more particularly to a compound and a derivative shown in a formula I and a preparation method and application thereof.
Background
The exploration and discovery of the pesticide active compound not only has a new structure, but also has a new target, and is the focus of research and attention of the current new pesticide creation. In the metabolic process of organisms, pyruvate dehydrogenase complex catalyzes the conversion of pyruvate into acetyl-CoA in organisms, and is a key enzyme for connecting glycolysis and the citric acid cycle, and is also a key enzyme for the energy metabolic process in organisms. Therefore, the pyruvate dehydrogenase complex is an action target with important agronomic significance, and the reasonable design of pesticide molecules aiming at the target also has high research value. At present, some pyruvate dehydrogenase inhibitors are reported, for example, thiamine pyrophosphate analogues T-1 and T-2 are a class of reported documents, and aim at the pyruvate dehydrogenase high-efficiency inhibitors in microorganisms.
Although thiamine pyrophosphate analogs T-1 and T-2 are a class of highly effective inhibitors against the pyruvate dehydrogenase system in microorganisms. However, the compound has a complex structure and high synthesis difficulty, and the thiamine pyrophosphate analogue has no application value in agriculture; therefore, the applicant designed and synthesized a novel efficient inhibitor with pyruvate dehydrogenase as a target in microorganisms. In particular, the research is carried out to find a novel structural compound having application value in the aspects of agricultural bacteria and fungi. Has important research significance and application value for developing novel high-efficiency bactericides.
Disclosure of Invention
The present invention is directed to solving, at least to some extent, one of the technical problems in the related art. To this end, the object of the present invention is to propose a class of compounds having antibacterial activity.
In a first aspect of the invention, a compound is provided. According to an embodiment of the invention, the compound is a compound of formula I or an enantiomer, diastereomer, racemate, pharmaceutically acceptable salt, crystalline hydrate or solvate of the compound of formula I,
in the formula, R1Is hydrogen or iodine;
x represents O, S or NH;
y is carbonyl, sulfuryl or an optionally substituted aromatic heterocyclic group;
z is methyl, optionally substituted aromatic heterocyclic group, optionally substituted alkyl or optionally substituted phenyl;
n is 1,2, 3.
The inventors have surprisingly found that the compounds according to the examples of the present invention have effective antibacterial biological activity and activity against cyanobacteria.
According to an embodiment of the invention, the above-mentioned compounds may also have the following additional technical features:
according to one embodiment of the invention, Y is a carbonyl group, a sulfone group,
According to one embodiment of the invention, Z is methyl, optionally substituted phenyl,furyl, thienyl, wherein,
R2is methyl or trifluoromethyl;
R3is amino or methylamino.
According to one embodiment of the invention, Z is methyl, phenyl substituted with 1-2 nitro groups, phenyl substituted with 1-3 halogen groups, phenyl substituted with 1-3 methyl groups, phenyl substituted with methoxy groups,Furyl, thienyl, wherein R2Is methyl or trifluoromethyl;
R3is amino or methylamino.
Optionally, the halogen is fluorine, chlorine, bromine or iodine.
In one embodiment of the present invention, Z is methyl, phenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 3, 5-dinitrophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-chlorophenyl, 3-chlorophenyl, 2, 4-dichlorophenyl, 4-fluorophenyl, 3-fluorophenyl, 2, 4-difluorophenyl, 3-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2, 4-dimethylphenyl, 2,4, 6-trimethylphenyl, 3-nitro-4-chlorophenyl, 2-chloro-4-nitrophenyl, 2-nitro-4-chlorophenyl, 2-chloro-4-nitrophenyl, 2-chlorophenyl, 4-chlorophenyl, or,A furyl group, a thienyl group,
wherein,
R2is methyl or trifluoromethyl;
R3is amino or methylamino.
According to one embodiment of the present invention, the compound is the following compound or an enantiomer, a diastereomer, a racemate, a pharmaceutically acceptable salt, a crystalline hydrate or a solvate of the following compound:
in a second aspect of the invention, there is provided a process for the preparation of a compound as hereinbefore described, which process, according to an embodiment of the invention, comprises:
contacting a compound of formula II with a compound of formula III to obtain a compound of formula I.
Wherein X, Y, Z, n, R1、R2、R3Is as defined in any one of claims 1 to 6.
According to the embodiment of the invention, the contact is carried out by dissolving the compound shown in the formula II and the compound shown in the formula III in a first organic solvent, adding a catalyst and an organic base and stirring,
optionally, the molar ratio of the compound shown in the formula II to the compound shown in the formula III, the catalyst and the organic base is 1:1-1.5: 0.01-0.15: 0.5 to 2;
optionally, the first organic solvent is at least one of acetonitrile, 1, 2-dichloroethane, acetone, tert-butanol, water, toluene, benzene, xylene, ethyl acetate, N-hexane, dichloromethane, chloroform, tetrahydrofuran, dimethyl sulfoxide, or N, N-dimethylformamide;
optionally, the catalyst is CuSO4·5H2O, sodium ascorbate, CuBr (PPh)3)3CuBr, CuI, or Cu (OAc)2At least one of;
optionally, the organic base is at least one of triethylamine, diethylamine, DMAP, diisopropylethylamine, N-methylmorpholine, pyridine, or piperidine.
Thus, in accordance with the examples of the present invention, the present invention provides a synthetic route that can be used to prepare compounds of formula I
Dissolving 2-methyl 4-amino-5-methyl azidopyrimidine (a compound shown in a formula II) and 1.5 equivalents of amine propyne in 6mL of solvent of tert-butyl alcohol and water (the volume ratio of the tert-butyl alcohol to the water is 2: 1), respectively adding 0.01mmol of blue vitriol and 0.1mmol of sodium ascorbate, stirring and reacting at 0 ℃ for 24h, adding 50mL of water after the reaction is finished, stirring to precipitate a solid, performing suction filtration, and drying to obtain a yellow solid.
In a third aspect of the invention, there is provided a pesticide comprising a compound as hereinbefore described. The inventors found that the pesticide can be effectively used for antibacterial.
In a fourth aspect of the invention, there is provided a method of treatment or prophylaxis of a plant disease caused by at least one of the following: rice bacterial brown spot pathogen, rice bacterial leaf blight pathogen, optionally, the plant is rice.
In a fifth aspect of the invention, there is provided a method of removing cyanobacteria with a compound or pesticide as hereinbefore described.
Detailed Description
The following describes embodiments of the present invention in detail. The embodiments described below by reference are exemplary and are intended to be illustrative of the invention, but are not to be construed as limiting the invention.
Example 1
Preparation of Compound 1
Dissolving 1mmol of 2-methyl 4-amino-5-methyl azidopyrimidine and 1mmol of 4-chlorobenzenesulfonamide propyne in a solvent of 6mL of tertiary butanol and water (the volume ratio of the tertiary butanol to the water is 2: 1), respectively adding 0.01mmol of copper sulfate pentahydrate and 0.1mmol of sodium ascorbate, stirring at 0 ℃ for 24 hours, adding 50mL of water after the reaction is finished, stirring to separate out solids, performing suction filtration, drying to obtain yellow solids, adding the yellow solids into 5mL of concentrated hydrochloric acid, stirring at room temperature until the system is clear, and removing redundant hydrochloric acid under reduced pressure to obtain a yellow solid target compound with the yield of 86% and mp 161-164 ℃;
elemental analysis/%: calculated values: c, 41.87; h, 3.98; n, 22.79; found C, 41.68; h, 3.69; n, 22.66;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),4.06(s,2H,CH2),5.62(s,2H,CH2),7.64(d,2H,NH2,J＝6.6Hz),7.78(s,2H,Ar-H),8.24(s,1H,1,2,3-triazol-4-yl-H),8.29(s,1H,Ar-H),8.40(s,1H,Ar-H),8.89(s,1H,pyrimidin-5-yl-H),9.23(s,1H,NH),14.85(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):20.72,37.10,44.88,108.79,124.86,127.75,128.56,132.56,136.24,138.15,143.08,160.28,161.94；
ESI-MS m/z:394.3(M-Cl)+
compounds 2-12 were prepared analogously to Compound 1 and have the following structural identification data:
example 2
The pure product is yellow solid, the yield is 88 percent, and the purity is m.p.157-159 ℃;
elemental analysis/%: calculated values: c, 43.53; h, 4.14; n, 23.69; measured value: c, 43.66; h, 4.43; n, 23.55;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),4.06(s,2H,CH2),5.61(s,2H,CH2),7.66(s,2H,NH2),7.79(s,2H,Ar-H),8.24(s,1H,1,2,3-triazol-4-yl-H),8.30(s,1H,Ar-H),8.40(s,1H,Ar-H),8.89(s,1H,pyrimidin-5-yl-H),9.24(s,1H,NH),14.85(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):20.39,36.51,44.47,108.05,125.05,127.18,128.05,132.25,135.56,137.41,142.61,159.59,161.24；
ESI-MS m/z:405.3(M-Cl)+；
example 3
The pure product is yellow solid, the yield is 85 percent, and the purity is m.p.125-126 ℃;
elemental analysis/%: calculated values: c, 40.87; h, 3.89; n,25.42 measurement: c, 40.77; h, 3.55; n,25.66
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),4.13(s,2H,CH2),5.55(s,2H,CH2),8.02(d,2H,NH2,J＝7.6Hz),8.20(s,1H,1,2,3-triazol-4-yl-H),8.37(d,3H,Ar-H,J＝7.7Hz),8.67(s,1H,Ar-H),8.77(s,1H,pyrimidin-5-yl-H),9.23(s,1H,NH),14.52(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):21.00,38.98,46.63,109.01,124.19,127.93,141.67,145.49,146.62,149.09,160.81,162.41；
ESI-MS m/z:405.3(M-Cl)+；
Example 4
The pure product is yellow solid, the yield is 86 percent, and the m.p.29-30 ℃;
elemental analysis/%: calculated values: c, 35.98; h, 4.83; n, 29.37; measured value: c, 35.78; h, 4.66; n, 29.23;
1H NMR(400MHz,DMSO-d6)(ppm):2.57(s,3H,CH3),2.91(s,3H,CH3),4.24(s,2H,CH2),5.63(s,2H,CH2),8.35(s,2H,NH2),7.59(s,1H,1,2,3-triazol-4-yl-H),8.77(s,1H,pyrimidin-5-yl-H),9.22(s,1H,NH),14.49(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):18.07,33.60,36.71,42.51,104.83,125.10,134.56,140.14,156.75,158.27；
ESI-MS m/z:298.4(M-Cl)+；
example 5
The pure product is yellow solid, the yield is 89 percent, and the purity is m.p.156-158 ℃;
elemental analysis/%: calculated values: c, 46.88; h, 4.92; n, 23.92; measured value: c, 46.66; h, 4.55; n, 23.88;
1H NMR(400MHz,DMSO-d6)(ppm):2.39(s,3H,CH3),2.53(s,3H,CH3),4.00(s,2H,CH2),5.64(s,2H,CH2),7.39(d,2H,NH2,J＝7.5Hz),7.69(d,2H,Ar-H,J＝7.4Hz),8.18(s,1H,1,2,3-triazol-4-yl-H),8.24(s,1H,Ar-H),8.31(s,1H,Ar-H),8.92(s,1H,pyrimidin-5-yl-H),9.24(s,1H,NH),14.94(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):20.42,20.69,36.80,44.91,108.45,125.55,128.67,135.71,135.85,140.87,141.45,142.90,159.99,161.64；
ESI-MS m/z:374.4(M-Cl)+；
example 6
The pure product is yellow solid, the yield is 86 percent, and the purity is m.p.142-143 ℃;
elemental analysis/%: calculated values: c, 45.51; h, 4.58; n, 24.77; measured value: c, 45.65; h, 4.76; n, 24.89;
1H NMR(400MHz,DMSO-d6)(ppm):2.50(s,3H,CH3),4.01(s,2H,CH2),5.58(s,2H,CH2),7.54(d,2H,NH2,J＝6.7Hz),7.58(d,1H,Ar-H,J＝6.4Hz),7.75(d,2H,Ar-H,J＝6.8Hz),8.14(s,1H,1,2,3-triazol-4-yl-H),8.25(s,2H,Ar-H),8.87(s,1H,pyrimidin-5-yl-H),9.20(s,1H,NH)；14.93(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):20.81,37.06,44.94,108.69,122.30,125.65,128.45,131.75,133.76,139.10,143.11,160.20,161.86；
ESI-MS m/z:360.3(M-Cl)+；
example 7
The pure product is yellow solid, the yield is 89 percent, and the purity is m.p.178-179 ℃;
elemental analysis/%: calculated values: c, 37.95; h, 3.61; n, 20.65; measured value: c, 37.89; h, 3.57; n, 20.54.;
1H NMR(400MHz,DMSO-d6)(ppm):2.61(s,3H,CH3),4.14(s,2H,CH2),5.70(s,2H,CH2),7.81(d,2H,NH2,J＝7.9Hz),7.88(d,2H,Ar-H,J＝8.0Hz),8.32(s,1H,1,2,3-triazol-4-yl-H),8.38(s,1H,Ar-H),8.51(s,1H,Ar-H),9.00(s,1H,pyrimidin-5-yl-H),9.33(s,1H,NH),15.01(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):20.96,37.38,45.12,109.11,124.89,125.63,127.06,128.12,131.75,138.83,143.29,160.55,162.22；
ESI-MS m/z:440.2(M-Cl)+；
example 8
The pure product is yellow solid, the yield is 91 percent, and the purity is m.p.106-108 ℃;
elemental analysis/%: calculated values: c, 49.37; h, 5.52; n, 22.39; measured value: c, 49.55; h, 5.66; n, 22.66;
1H NMR(400MHz,DMSO-d6)(ppm):2.24(s,3H,CH3),2.53(s,9H,3CH3),4.03(s,2H,CH2),5.56(s,2H,CH2),6.98(d,2H,NH2,J＝8.8Hz),8.02(d,1H,Ar-H,J＝8.0Hz),8.11(s,1H,1,2,3-triazol-4-yl-H),8.27(s,1H,Ar-H),8.84(s,1H,pyrimidin-5-yl-H),9.24(s,1H,NH),14.82(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):19.26,20.28,21.22,35.38,44.42,108.02,125.69,130.00,132.52,135.28,136.45,139.55,142.34,159.48,161.13；
ESI-MS m/z:402.4(M-Cl)+；
example 9
The obtained pure product is yellow solid, the yield is 90 percent, and the purity is m.p.134-135 ℃;
elemental analysis/%: calculated values: c, 45.12; h, 4.73; n, 23.02; measured value: c, 45.55; h, 4.92; n, 23.43;
1H NMR(400MHz,DMSO-d6)(ppm):2.54(s,3H,CH3),3.86(s,3H,OCH3),4.00(s,2H,CH2),5.66(s,2H,CH2),7.11(s,2H,NH2),7.74(d,2H,Ar-H,J＝4.5Hz),8.09(s,1H,1,2,3-triazol-4-yl-H),8.29(s,2H,Ar-H),8.90(s,1H,pyrimidin-5-yl-H),9.24(s,1H,NH),14.85(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):20.25,36.19,44.43,55.04,107.72,112.80,125.95,127.11,129.68,131.62,142.39,159.34,160.09,160.97；
ESI-MS m/z:390.4(M-Cl)+；
example 10
The pure product is yellow solid, the yield is 89 percent, and the purity is m.p.103-105 ℃;
elemental analysis/%: calculated values: c, 40.87; h, 3.89; n, 25.42; measured value: c, 40.80; h, 3.99; n, 25.49;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),4.23(s,2H,CH2),5.57(s,2H,CH2),7.82(d,2H,NH2,J＝7.2Hz),7.94(d,2H,Ar-H,J＝7.3Hz),8.14(s,1H,1,2,3-triazol-4-yl-H),8.29(s,1H,Ar-H),8.77(s,1H,pyrimidin-5-yl-H),8.85(s,1H,Ar-H),9.22(s,1H,NH),14.84(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):20.80,37.25,44.86,108.83,123.71,124.65,128.85,131.89,132.06,133.42,140.03,143.18,146.49,160.35,161.98；
ESI-MS m/z:405.3(M-Cl)+；
example 11
The pure product is yellow solid, the yield is 89 percent, and the purity is m.p.81-83 ℃;
elemental analysis/%: calculated values: c, 40.87; h, 3.89; n, 25.42; measured value: c, 40.86; h, 3.99; n, 25.44.;
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),4.14(s,2H,CH2),5.54(s,2H,CH2),7.86(t,1H,Ar-H,J＝7.9Hz),8.13-8.18(m,2H,NH2),8.28(s,1H,1,2,3-triazol-4-yl-H),8.43-8.47(m,2H,Ar-H),8.69(s,1H,Ar-H),8.83(s,1H,pyrimidin-5-yl-H),9.22(s,1H,NH),14.77(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):21.03,37.70,45.19,109.48,120.68,121.24,126.83,131.06,132.45,133.55,141.92,143.70,147.42,161.08,162.70；
ESI-MS m/z:405.4(M-Cl)+；
example 12
The obtained pure product is white solid, the yield is 89%, and the m.p.103-105 ℃;
elemental analysis/%: calculated values: c, 37.90; h, 3.39; n, 23.57; measured value: c, 37.88; h, 3.42; n, 23.55;
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),4.15(s,2H,CH2),5.58(s,2H,CH2),8.02(d,2H,NH2,J＝10.7Hz),8.23(s,1H,Ar-H),8.31(s,1H,1,2,3-triazol-4-yl-H),8.41(s,1H,Ar-H),8.70(s,1H,pyrimidin-5-yl-H),8.82(s,1H,Ar-H),9.22(s,1H,NH),14.66(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):20.55,36.91,44.69,108.54,121.05,123.05,128.16,130.56,132.18,139.48,143.04,146.04,160.23,161.83；
ESI-MS m/z:439.2(M-Cl)+；
example 13
Preparation of Compound 13
Dissolving 1mmol of 2-methyl-4-amino-5-methyl azidopyrimidine and 2mmol of iodo-4-chlorobenzenesulfonamide propyne in 5ml of anhydrous tetrahydrofuran, respectively adding 0.05mmol of CuI and 2mmol of triethylamine, stirring and reacting at 25-30 ℃ for 12h, adding water, stirring to separate out a solid, performing suction filtration, drying to obtain a yellow solid, adding the yellow solid into 5ml of concentrated hydrochloric acid, stirring at room temperature until the system is clear, and removing redundant hydrochloric acid under reduced pressure to obtain a yellow solid target compound with the yield of 78%, mp: 146-147 ℃;
elemental analysis/%: calculated values: c, 32.39; h, 2.90; n, 17.63; measured value: c, 32.42; h, 3.10; n, 17.83;
1H NMR(400MHz,DMSO-d6)(ppm):2.54(s,3H,CH3),4.01(s,2H,CH2),5.45(s,2H,CH2),7.67(d,2H,NH2,J＝7.3Hz),7.79-7.87(m,3H,Ar-H),8.34(s,1H,Ar-H),8.72(s,1H,pyrimidin-5-yl-H),9.28(s,1H,NH),14.70(s,1H,HCl)；
ESI-MS m/z:520.3(M-Cl)+；
compounds 14-22 were prepared analogously to Compound 13 and have the following structure identification data:
example 14
The obtained pure product is yellow solid, the yield is 90 percent, and the purity is m.p.155-157 ℃;
elemental analysis/%: calculated values: c, 33.38; h, 2.99; n, 18.17; measured value: c, 33.51; h, 3.12; n, 18.47;
1H NMR(400MHz,DMSO-d6)(ppm):2.51(s,3H,CH3),3.98(s,2H,CH2),5.43(s,2H,CH2),7.63(s,2H,NH2),7.75-7.79(m,3H,Ar-H),8.31(s,1H,Ar-H),8.72(s,1H,pyrimidin-5-yl-H),9.25(s,1H,NH),14.77(s,1H,HCl)；
ESI-MS m/z:504.3(M-Cl)+；
example 15
The obtained pure product is light yellow solid, the yield is 85 percent, and the m.p.158-160 ℃;
elemental analysis/%: calculated values: c, 31.79; h, 2.85; n, 19.77; measured value: c, 31.85; h, 3.12; n, 20.11;
1H NMR(400MHz,DMSO-d6)(ppm):2.51(s,3H,CH3),4.04(s,2H,CH2),5.42(s,2H,CH2),7.78(s,1H,Ar-H),8.02(d,2H,NH2,J＝7.9Hz),8.38(d,2H,Ar-H,J＝8.2Hz),8.62(s,1H,Ar-H),8.70(s,1H,pyrimidin-5-yl-H),9.25(s,1H,NH),14.79(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.41,160.81,149.09,146.62,145.49,141.67,127.93,124.19,109.01,46.63,40.22,40.01,39.81,39.60,39.39,39.19,38.98,37.95,21.00；ESI-MS m/z:531.2(M-Cl)+；
example 16
The pure product is yellow solid, the yield is 89 percent, and the m.p.128-129 ℃;
elemental analysis/%: calculated values: c, 26.13; h, 3.29; n, 21.33; measured value: c, 26.35; h, 3.52; n, 21.65.;
1H NMR(400MHz,DMSO-d6)(ppm):2.55(s,3H,CH3),2.93(s,3H,CH3),4.19(s,2H,CH2),5.50(s,2H,CH2),7.54(s,1H,NH2),7.87(s,1H,NH2),8.77(s,1H,pyrimidin-5-yl-H),9.28(s,1H,NH),14.78(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):161.12,159.49,140.70,107.63,45.84,44.66,36.79,20.44；
ESI-MS m/z:424.1(M-Cl)+；
example 17
The pure product is yellow solid, the yield is 95 percent, and the purity is m.p.155-157 ℃;
elemental analysis/%: calculated values: c, 35.87; h, 3.57; n, 18.30; measured value: c, 35.99; h, 3.68; n, 18.65.;
1H NMR(400MHz,DMSO-d6)(ppm):2.40(s,3H,CH3),2.56(s,3H,CH3),3.96(s,2H,CH2),5.48(s,2H,CH2),7.41(d,2H,NH2,J＝6.1Hz),7.71(d,2H,Ar-H,J＝6.1Hz),7.80(s,1H, Ar-H),8.10(s,1H,Ar-H),8.77(s,1H,pyrimidin-5-yl-H),9.30(s,1H,NH),14.76(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):161.92,160.34,141.89,141.28,136.18,128.92,125.89,108.56,46.35,37.54,20.85,20.64；
ESI-MS m/z:500.2(M-Cl)+；
example 18
The obtained pure product is yellow solid, the yield is 91 percent, and the purity is m.p.115-116 ℃;
elemental analysis/%: calculated values: c, 37.05; h, 3.52; n, 20.16; measured value: c, 37.36; h, 3.66; n, 20.54.;
1H NMR(400MHz,DMSO-d6)(ppm):2.54(s,3H,CH3),3.99(s,2H,CH2),5.43(s,2H,CH2),7.58(s,2H,NH2),7.63(s,1H,Ar-H),7.79(s,2H,Ar-H),8.21-8.29(m,1H,Ar-H),8.67(s,1H,pyrimidin-5-yl-H),9.28(s,1H,NH)；14.51(s,1H,HCl)；
ESI-MS m/z:486.2(M-Cl)+；
example 19
The obtained pure product is light yellow solid, the yield is 89%, and the m.p.159-160 ℃;
elemental analysis/%: calculated values: c, 29.99; h, 2.68; n, 16.32.; measured value: c, 30.11; h, 2.98; n, 16.52;
1H NMR(400MHz,DMSO-d6)(ppm):2.55(s,3H,CH3),4.01(s,2H,CH2),5.47(s,2H,CH2),7.73(d,2H,Ar-H,J＝7.5Hz),7.81(s,1H,Ar-H),7.83(s,2H,NH2),8.36(s,1H,Ar-H),8.77(s,1H,pyrimidin-5-yl-H),9.30(s,1H,NH),14.89(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.97,161.34,147.08,142.15,139.59,132.35,128.86,126.49,109.59,47.22,38.43,21.43；
ESI-MS m/z:566.1(M-Cl)+；
example 20
The pure product is yellow solid, the yield is 91 percent, and the m.p.185-186 ℃;
elemental analysis/%: calculated values: c, 40.92; h, 4.39; n, 18.56; measured value: c, 40.85; h, 4.15; n, 18.66.;
1H NMR(400MHz,DMSO-d6)(ppm):2.25(s,3H,CH3),2.53(s,3H,CH3),2.55(s,6H,2CH3),3.96(s,2H,CH2),5.43(s,2H,CH2),6.99(s,2H,NH2),7.77(s,1H,Ar-H),7.96(s,1H,Ar-H),8.67(s,1H,pyrimidin-5-yl-H),9.29(s,1H,NH),14.67(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.65,161.13,147.32,141.37,138.45,133.94,131.55,109.54,46.75,37.41,22.70,21.17,20.51；
ESI-MS m/z:528.3(M-Cl)+；
example 21
The pure product is yellow solid, the yield is 87 percent, and the purity is m.p.140-142 ℃;
elemental analysis/%: calculated values: c, 37.22; h, 3.71; n, 18.99; measured value: c, 37.00; h, 3.56; and N,19.25.
1H NMR(400MHz,DMSO-d6)(ppm):2.55(s,3H,CH3),3.86(s,3H,OCH3),3.94(s,2H,CH2),5.48(s,2H,CH2),7.11(s,2H,NH2),7.74(s,2H,Ar-H),7.81(s,2H,Ar-H),8.01(s,2H,Ar-H),8.76(s,1H,pyrimidin-5-yl-H),9.30(s,1H,NH),14.84(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):161.66,160.96,160.08,141.05,130.44,127.81,113.40,108.28,55.38,46.11,37.31,20.68；
ESI-MS m/z:516.3(M-Cl)+；
Example 22
The pure product is yellow solid, the yield is 87 percent, and the purity is m.p.148-150 ℃;
elemental analysis/%: calculated values: c, 33.91; h, 3.04; n, 21.09; measured value: c, 34.12; h, 3.25; n, 21.35.;
1H NMR(400MHz,DMSO-d6)(ppm):2.50(s,3H,CH3),4.14(s,2H,CH2),5.40(s,2H,CH2),7.80(s,2H,NH2),7.90(d,3H,Ar-H,J＝12.5Hz),8.65(s,1H,Ar-H),8.69(s,1H,pyrimidin-5-yl-H),9.24(s,1H,NH),14.59(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):156.27,154.85,140.95,136.67,129.11,127.56,126.23,123.51,119.27,102.77,41.93,32.77,17.54；
ESI-MS m/z:531.3(M-Cl)+；
example 23
Preparation of Compound 23
Dissolving 1mmol of 2-methyl-4-amino-5-methyl azidopyrimidine and 1.5mmol of benzoyl ester butyne in a solvent of 6mL of DMF, respectively adding 0.15mmol of CuI and 2mmol of pyridine, stirring at 100 ℃ for reaction for 1h, adding 50mL of water after the reaction is finished, stirring to separate out a solid, performing suction filtration, drying to obtain a white solid, adding the white solid into 5mL of concentrated hydrochloric acid, stirring at room temperature until the system is clear, and removing redundant hydrochloric acid under reduced pressure to obtain a yellow solid target compound with the yield of 95%, mp: 135 ℃ and 137 ℃;
elemental analysis/%: calculated values: c, 54.47; h, 5.11; n, 22.42; measured value: c, 54.66; h, 5.32; n, 22.10.;
1H NMR(400MHz,DMSO-d6)(ppm):2.50(s,3H,CH3),3.11(s,2H,CH2),4.49(s,2H,CH2),5.62(s,2H,CH2),7.52(s,2H,NH2),7.65(s,1H,Ar-H),7.91(d,2H,Ar-H,J＝6.1Hz),8.29(s,2H,Ar-H),8.84(s,1H,1,2,3-triazol-4-yl-H),9.18(s,1H,pyrimidin-5-yl-H),14.79(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):164.10,161.57,159.76,142.99,132.22,128.00,127.89,127.66,108.18,62.19,45.07,23.72,20.50；
ESI-MS m/z:339.0(M-Cl)+；
compounds 24-40 were prepared analogously to Compound 23, and the structural identification data are as follows:
example 24
The obtained pure product is yellow solid, the yield is 98 percent, and the purity is m.p.141-142 ℃;
elemental analysis/%: calculated values: c, 48.64; h, 4.32; n, 23.35; measured value: c, 48.32; h, 4.22; n, 23.12;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),3.18(s,2H,CH2),4.58(s,2H,CH2),5.68(s,2H,CH2),8.17(s,2H,NH2),8.32-8.44(m,4H,Ar-H),8.90(s,1H,pyrimidin-5-yl-H),9.21(s,1H,1,2,3-triazol-4-yl-H),14.76(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):163.17,162.10,160.32,149.21,143.30,135.36,133.98,129.97,123.20,122.94,108.78,63.46,45.23,24.06,20.65；
ESI-MS m/z:384.3(M-Cl)+；
example 25
The obtained pure product is yellow solid, the yield is 98 percent, and the m.p.129-131 ℃;
elemental analysis/%: calculated values: c, 48.64; h, 4.32; n, 23.35; measured value: c, 48.66; h, 4.21; n, 23.22;
1H NMR(400MHz,DMSO-d6)(ppm):2.50(s,3H,CH3),3.06(s,2H,CH2),4.50(s,2H,CH2),5.64(s,2H,CH2),7.82(s,2H,NH2),7.84(d,1H,Ar-H,J＝6.6Hz),8.03(d,1H,Ar-H,J＝7.6Hz),8.22(s,1H,Ar-H),8.28(s,1H,Ar-H),8.89(s,1H,pyrimidin-5-yl-H),9.18(s,1H,1,2,3-triazol-4-yl-H),15.11(s,1H,HCl)；
ESI-MS m/z:384.3(M-Cl)+；
example 26
The pure product is yellow solid, the yield is 90 percent, and the purity is m.p.189-191 ℃;
elemental analysis/%: calculated values: c, 49.89; h, 4.43; n, 20.53; measured value: c, 50.11; h, 4.44; n, 20.88;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),3.13(s,2H,CH2),4.54(s,2H,CH2),5.64(s,2H,CH2),7.48(s,1H,Ar),7.58(s,2H,NH2),7.76(d,1H,Ar-H,J＝7.2Hz),8.31(d,2H,Ar-H,J＝13.7Hz),8.87(s,1H,pyrimidin-5-yl-H),9.22(s,1H,1,2,3-triazol-4-yl-H),14.82(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):163.52,161.75,159.95,143.10,132.30,130.51,130.09,129.74,128.57,126.52,108.41,62.96,44.98,23.75,20.54；
ESI-MS m/z:373.3(M-Cl)+；
example 27
The pure product is yellow solid, the yield is 91 percent, and the m.p. is 150-152 ℃;
elemental analysis/%: calculated values: c, 49.70; h, 4.17; n, 23.46; measured value: c, 49.87; h, 4.36; n,23.88.
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),3.12(s,2H,CH2),4.52(s,2H,CH2),5.68(s,2H,CH2),7.26(s,1H,Ar-H),7.44(t,1H,Ar-H,J＝9.9Hz),7.95(d,1H,Ar-H,J＝6.8Hz),8.32(s,2H,NH2),8.93(s,1H,pyrimidin-5-yl-H),9.23(s,1H,1,2,3-triazol-4-yl-H),14.97(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.83,162.22,161.58,160.43,159.83,143.40,133.37,133.27,114.05,113.97,111.83,111.61,108.92,104.97,63.15,45.35,24.13,20.77；
ESI-MS m/z:375.3(M-Cl)+；
Example 28
The obtained pure product is yellow solid, the yield is 96 percent, and the purity is m.p.132-134 ℃;
elemental analysis/%: calculated values: c, 53.40; h, 5.23; n, 20.76; measured value: c, 53.55; h, 5.24; n, 20.88;1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),3.11(s,2H,CH2),3.85(s,3H,OCH3),4.46(s,2H,CH2),5.66(s,2H,CH2),7.06(d,2H,Ar-H,J＝8.4Hz),7.88(d,2H,Ar-H,J＝8.4Hz),8.32(s,2H,NH2),8.91(s,1H,pyrimidin-5-yl-H),9.23(s,1H,1,2,3-triazol-4-yl-H),14.86(s,1H,HCl)；
ESI-MS m/z:369.2(M-Cl)+；
example 29
The pure product is yellow solid, the yield is 92 percent, and the purity is m.p.86-88 ℃;
elemental analysis/%: calculated values: c, 51.98; h, 4.62; n, 21.39; measured value: c, 51.99; h, 4.68; n, 21.66.;1H NMR(400MHz,DMSO-d6)(ppm):2.54(s,3H,CH3),3.13(s,2H,CH2),4.53(s,2H,CH2),5.61(s,2H,CH2),7.35(s,2H,NH2),7.70(s,1H,Ar-H),7.85(s,1H,Ar-H),8.28(s,2H,Ar-H),8.78(s,1H,pyrimidin-5-yl-H),9.22(s,1H,1,2,3-triazol-4-yl-H),14.58(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):163.17,162.10,160.32,156.34,149.21,143.30,135.36,133.98,129.97,123.20,122.94,108.78,63.46,45.23,24.06,20.65；
ESI-MS m/z:357.2(M-Cl)+；
example 30
The obtained pure product is yellow solid, the yield is 95 percent, and the m.p.114-116 ℃;
elemental analysis/%: calculated values: c, 51.98; h, 4.62; n, 21.39; measured value: c, 51.66; h, 4.85; n, 21.55;
1H NMR(400MHz,DMSO-d6)(ppm):2.51(s,3H,CH3),3.13(s,2H,CH2),4.51(s,2H,CH2),5.60(s,2H,CH2),7.37(t,2H,Ar-H,J＝8.0Hz),7.99(s,2H,NH2),8.29(s,2H,Ar-H),8.79(s,1H,pyrimidin-5-yl-H),9.22(s,1H,1,2,3-triazol-4-yl-H),14.53(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):168.71,163.00,161.38,160.51,159.88,158.43,141.10,129.22,122.89,113.26,113.06,106.74,60.37,44.08,22.20,19.23；
ESI-MS m/z:357.3(M-Cl)+；
example 31
The obtained pure product is yellow solid, the yield is 92 percent, and the m.p.99-100 ℃;
elemental analysis/%: calculated values: c, 49.89; h, 4.43; n, 20.53; measured value: c, 50.11; h, 4.35; and N,20.65.
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),3.12(s,2H,CH2),4.50(s,2H,CH2),5.59(s,2H,CH2),7.62(d,2H,NH2,J＝8.0Hz),7.92(d,2H,Ar-H,J＝8.0Hz),8.23(s,1H,Ar-H),8.32(s,1H,Ar-H),8.81(s,1H,pyrimidin-5-yl-H),9.22(s,1H,1,2,3-triazol-4-yl-H),14.59(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):164.54,162.80,161.02,143.69,138.02,130.81,128.80,128.15,109.50,63.59,45.39,24.65,21.00；
ESI-MS m/z:373.4(M-Cl)+；
Example 32
The pure product is yellow solid, the yield is 94 percent, and the m.p.176-178 ℃;
elemental analysis/%: calculated values: c, 46.02; h, 3.86; n, 18.94; measured value: c, 46.35; h, 3.98; n, 18.99.;
1H NMR(400MHz,DMSO-d6)(ppm):2.43(s,3H,CH3),3.07(s,2H,CH2),4.47(s,2H,CH2),5.66(s,2H,CH2),7.46(s,1H,Ar-H),7.58(s,1H,Ar-H),7.69(s,1H,Ar-H),8.23(s,2H,NH2),8.79(s,1H,pyrimidin-5-yl-H),9.12(s,1H,1,2,3-triazol-4-yl-H),14.75(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):161.68,160.95,159.15,142.77,135.17,131.29,128.53,126.24,126.15,107.49,62.49,44.76,23.18,20.23；
ESI-MS m/z:407.4(M-Cl)+；
example 33
The pure product is yellow solid, the yield is 95 percent, and the m.p.126-129 ℃;
elemental analysis/%: calculated values: c, 49.89; h, 4.43; n, 20.53; measured value: c, 50.12; h, 4.52; n, 20.63;
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),3.14(s,2H,CH2),4.37(s,2H,CH2),5.16(s,2H,CH2),7.59(s,1H,Ar-H),7.75(d,1H,Ar-H,J＝6.4Hz),7.89(s,2H,Ar-H),8.30(s,2H,NH2),8.80(s,1H,pyrimidin-5-yl-H),9.21(s,1H,1,2,3-triazol-4-yl-H),14.64(s,1H,HCl)；
ESI-MS m/z:373.2(M-Cl)+；
example 34
The obtained pure product is yellow solid, the yield is 90 percent, and the purity is m.p.110-111 ℃;
elemental analysis/%: calculated values: c, 43.93; h, 3.69; n, 24.11; measured value: c, 44.11; h, 3.98; n, 24.32.;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),3.21(s,2H,CH2),4.65(s,2H,CH2),5.60(s,2H,CH2),8.30(s,2H,NH2),8.77(s,1H,Ar-H),8.88(s,2H,Ar-H),9.05(s,1H,pyrimidin-5-yl-H),9.16(s,1H,1,2,3-triazol-4-yl-H),14.64(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):161.99,161.39,160.30,147.33,143.05,131.59,127.92,121.66,108.75,64.19,45.10,23.86,20.59；
ESI-MS m/z:429.4(M-Cl)+；
example 35
The obtained pure product is yellow solid, the yield is 98 percent, and the m.p.109-110 ℃;
elemental analysis/%: calculated values: c, 48.64; h, 4.32; n, 23.35; measured value: c, performing phase inversion; h,; n,;
1H NMR(400MHz,DMSO-d6)(ppm):2.51(s,3H,CH3),3.18(s,2H,CH2),4.58(s,2H,CH2),5.58(s,2H,CH2),7.86(s,1H,Ar-H),8.23(s,1H,NH2),8.29(s,1H,NH2),8.34(d,1H,Ar-H,J＝6.5Hz),8.51(d,1H,Ar-H,J＝7.6Hz),8.59(s,1H,Ar-H),8.77(s,1H,pyrimidin-5-yl-H),9.19(s,1H,1,2,3-triazol-4-yl-H),14.56(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.27,161.48,159.74,146.19,142.81,134.11,129.71,129.50,126.57,122.01,108.12,62.90,44.98,23.52,20.35；
ESI-MS m/z:384.3(M-Cl)+；
example 36
The obtained pure product is yellow solid, the yield is 99 percent, and the m.p.99-100 ℃;
elemental analysis/%: calculated values: c, 44.95; h, 3.77; n, 21.58.; measured value: c, 45.32; h, 3.98; n, 22.00.;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),3.16(s,2H,CH2),4.61(s,2H,CH2),5.69(s,2H,CH2),8.02(d,1H,Ar-H,J＝7.8Hz),8.31(d,2H,Ar-H,J＝7.1Hz),8.37(s,2H,NH2),8.93(s,1H,pyrimidin-5-yl-H),9.22(s,1H,1,2,3-triazol-4-yl-H),14.76(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.93,162.28,160.51,148.44,143.55,134.76,131.87,131.64,124.70,122.03,108.95,64.21,45.37,24.14,20.82；
ESI-MS m/z:418.3(M-Cl)+；
example 37
The obtained pure product is yellow solid, the yield is 98 percent, and the m.p.98-99 ℃;
elemental analysis/%: calculated values: c, 45.00; h, 4.00; n, 18.52; measured value: c, 45.32; h, 4.23; n, 18.65.;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),3.15(s,2H,CH2),4.52(s,2H,CH2),5.65(s,2H,CH2),7.76(d,2H,Ar-H,J＝6.7Hz),7.85(d,2H,Ar-H,J＝6.4Hz),8.32(s,1H,NH2),8.40(s,1H,NH2),8.83(s,1H,pyrimidin-5-yl-H),9.22(s,1H,1,2,3-triazol-4-yl-H),14.65(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.19,160.39,158.63,142.10,129.78,128.95,126.00,124.93,106.92,61.19,44.44,22.68,19.72；
ESI-MS m/z:384.3(M-Cl)+；
example 38
The pure product is yellow solid, the yield is 96 percent, and the m.p.92-93 ℃;
elemental analysis/%: calculated values: c, 45.00; h, 4.00; n, 18.52; measured value: c, 45.32; h, 4.32; n, 18.65.;
1H NMR(400MHz,DMSO-d6)(ppm):2.56(s,3H,CH3),3.14(s,2H,CH2),4.56(s,2H,CH2),5.74(s,2H,CH2),7.88(s,1H,NH2),7.94(s,1H,NH2),8.02-8.06(m,2H,Ar-H),8.34(s,1H,Ar-H),8.52(s,1H,Ar-H),8.93(s,1H,pyrimidin-5-yl-H),9.24(s,1H,1,2,3-triazol-4-yl-H),14.87(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):164.27,162.71,161.47,159.68,142.88,134.88,134.32,131.40,130.12,130.00,126.95,120.42,108.15,62.62,44.97,23.55,20.45；
ESI-MS m/z:417.4(M-Cl)+；
example 39
The pure product is yellow solid, the yield is 96 percent, and the purity is m.p.188-190 ℃;
elemental analysis/%: calculated values: c, 47.30; h, 4.50; n, 22.07; measured value: c, 47.65; h, 4.65; n, 22.32.;
1H NMR(400MHz,DMSO-d6)(ppm):2.58(s,3H,CH3),3.16(s,2H,CH2),4.53(s,2H,CH2),5.71(s,2H,CH2),7.29(s,1H,thiophene-H),7.85(s,1H,thiophene-H),8.03(d,1H,thiophene-H,J＝3.6Hz),8.36(s,2H,NH2),8.95(s,1H,pyrimidin-5-yl-H),9.28(s,1H,1,2,3-triazol-4-yl-H),14.96(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.60,161.93,160.19,143.23,133.64,133.11,131.71,127.71,108.62,62.65,45.30,24.02,20.74；
ESI-MS m/z:345.3(M-Cl)+；
example 40
The pure product is yellow solid, the yield is 99 percent, and the m.p. is 189-190 ℃;
elemental analysis/%: calculated values: c, 49.39; h, 4.70; n, 23.04; measured value: c, 50.11; h, 4.68; n, 23.45.;
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),3.08(s,2H,CH2),4.47(s,2H,CH2),5.65(s,2H,CH2),6.71(d,1H,furan-H,J＝2.3Hz),7.31(d,1H,furan-H,J＝3.3Hz),7.99(s,1H,furan-H),8.27(s,1H,NH2),8.31(s,1H,NH2),8.92(s,1H,pyrimidin-5-yl-H),9.22(s,1H,1,2,3-triazol-4-yl-H),14.93(s,1H,HCl)；
13C NMR(100MHz,DMSO-d6)(ppm):162.86,161.08,157.62,147.74,143.76,143.45,118.61,112.34,109.63,63.15,45.61,24.75,21.09；
ESI-MS m/z:329.3(M-Cl)+；
EXAMPLE 41
Preparation of Compound 41
Dissolving 1mmol of 2-methyl-4-amino-5-methyl azidopyrimidine and 1mmol of benzoyl ester pentyne in 6mL of acetonitrile solvent, adding 0.01mmol of cuprous bromide and 2mmol of triethylamine, stirring at 0-10 ℃ for reaction for 5-7h, adding 50mL of water after the reaction is finished, stirring to separate out solids, performing suction filtration, and drying to obtain light yellow solids, wherein the yield is 76%, and the mp: 122-124 ℃;
elemental analysis/%: calculated values: c, 61.35; h, 5.72; n, 23.85; measured value: c, 61.56; h, 5.68; n, 23.65.;
1H NMR(400MHz,DMSO-d6)(ppm):2.50(s,3H,CH3),3.31(s,2H,CH2),4.54(s,2H,CH2),4.59(s,2H,CH2),5.72(s,2H,CH2),7.34(s,2H,NH2),7.55(s,1H,Ar-H),7.96(d,2H,Ar-H,J＝6.1Hz),8.55(s,2H,Ar-H),8.94(s,1H,1,2,3-triazol-4-yl-H),9.19(s,1H,pyrimidin-5-yl-H)；ESI-MS m/z:353.2(M+H)+；
compounds 42-46 were prepared analogously to Compound 41 and have the following structural identification data:
example 42
The obtained pure product is green solid, the yield is 88 percent, and the m.p.186-188 ℃;
elemental analysis/%: calculated values: c, 62.28; h, 6.05; n, 22.94.; measured value: c, 62.59; h, 6.34; and N,22.99.
1H NMR(400MHz,DMSO-d6)(ppm):2.51(s,3H,CH3),2.59(s,3H,CH3),3.26(s,2H,CH2),4.49(s,2H,CH2),4.99(s,2H,CH2),5.58(s,2H,CH2),7.31(d,2H,Ar-H,J＝5.3Hz),7.65(s,2H,NH2),8.01(s,2H,Ar-H)；8.88(s,1H,pyrimidin-5-yl-H),9.21(s,1H,1,2,3-triazol-4-yl-H)；
ESI-MS m/z:367.3(M+H)+；
Example 43
The obtained pure product is white solid, the yield is 75 percent, and the m.p.124-125 ℃;
elemental analysis/%: calculated values: c, 55.89; h, 4.95; n, 21.73.; measured value: c, 56.11; h, 5.11; and N,21.98.
1H NMR(400MHz,DMSO-d6)(ppm):2.38(s,3H,CH3),3.12(s,2H,CH2),4.55(s,2H,CH2),4.65(s,2H,CH2)，5.68(s,2H,CH2),7.32(s,2H,NH2),7.88(s,2H,Ar-H),7.97(s,2H,Ar-H)；8.80(s,1H,pyrimidin-5-yl-H),9.21(s,1H,1,2,3-triazol-4-yl-H)；
ESI-MS m/z:387.2(M+H)+；
Example 44
The obtained pure product is yellow solid, the yield is 89%, and the m.p.120-122 ℃;
elemental analysis/%: calculated values: c, 50.13; h, 4.44; n, 19.49.; measured value: c, 50.51; h, 4.56; n,19.65.
1H NMR(400MHz,DMSO-d6)(ppm):2.36(s,3H,CH3),3.12(s,2H,CH2),4.52(s,2H,CH2),4.95(s,2H,CH2),5.68(s,2H,CH2),6.97(s,2H,NH2),7.88(s,2H,Ar-H),7.96(s,2H,Ar-H)；8.81(s,1H,pyrimidin-5-yl-H),9.21(s,1H,1,2,3-triazol-4-yl-H)；
ESI-MS m/z:431.1(M+H)+；
Example 45
The obtained pure product is yellow solid, the yield is 70 percent, and the m.p.124-125 ℃;
elemental analysis/%: calculated values: c, 54.40; h, 4.82; n, 24.67.; measured value: c, 54.96; h, 5.11; n,24.98.
1H NMR(400MHz,DMSO-d6)(ppm):2.35(s,3H,CH3),3.11(s,2H,CH2),4.64(s,2H,CH2),4.97(s,2H,CH2),5.46(s,2H,CH2),6.99(s,2H,NH2),8.22(s,1H,pyrimidin-5-yl-H),8.34(d,2H,Ar-H,J＝7.5Hz),8.39(d,2H,Ar-H,J＝8.2Hz),8.90(s,1H,pyrimidin-5-yl-H),9.21(s,1H,1,2,3-triazol-4-yl-H)；
ESI-MS m/z:398.1(M+H)+；
Example 46
The obtained pure product is green solid, the yield is 81 percent, and the purity is m.p.124-125 ℃;
elemental analysis/%: calculated values: c, 58.37; h, 5.17; n, 22.69.; measured value: c, 58.35; h, 5.56; n,22.98.
1H NMR(400MHz,DMSO-d6)(ppm):2.51(s,3H,CH3),3.22(s,2H,CH2),4.65(s,2H,CH2),4.98(s,2H,CH2),5.64(s,2H,CH2),7.03(s,2H,NH2),7.32(s,2H,Ar-H),7.95(s,2H,Ar-H)；8.79(s,1H,pyrimidin-5-yl-H),9.22(s,1H,1,2,3-triazol-4-yl-H)；
ESI-MS m/z:371.3(M+H)+；
Example 47
Preparation of Compound 47
1mmol of 2-methyl-4-amino-5-methylazidopyrimidine and 1mmol of iodophenylbutylkyne were dissolved in 5mL of n-hexane, and 0.05mmol of Cu (OAc) was added2And 2mmol of pyridine, stirring and reacting for 12 hours at the temperature of 40-50 ℃, adding water, stirring to separate out solids, performing suction filtration, and drying to obtain yellow solids, wherein the yield is 86%, and the mp: 168-170 ℃;
elemental analysis/%: calculated values: c, 43.98; h, 3.69; n, 18.10; measured value: c, 44.21; h, 3.74; n,18.32.
1H NMR(400MHz,DMSO-d6)(ppm):2.50(s,3H,CH3),3.07(s,2H,CH2),4.53(s,2H,CH2),5.50(s,2H,CH2),7.16(s,2H,NH2),7.52–7.45(m,2H,Ar-H),7.62(d,1H,Ar-H,J＝6.8Hz),7.89(d,1H,Ar-H,J＝7.3Hz)；
13C NMR(100MHz,DMSO-d6)(ppm):164.10,161.57,159.76,142.99,132.22,128.00,127.89,127.66,108.18,62.19,45.07,23.72,20.50；
ESI-MS m/z:465.3(M+H)+；
Compounds 48-60 were prepared analogously to Compound 47 and have the following structure identification data:
example 48
The pure product is yellow solid, the yield is 76 percent, and the m.p.199-201 ℃;
elemental analysis/%: calculated values: c, 40.09; h, 3.17; n, 19.25.; measured value: c, 40.21; h, 3.23; n,19.35.
1H NMR(400MHz,DMSO-d6)(ppm):2.35(s,3H,CH3),3.11(s,2H,CH2),4.64(s,2H,CH2),5.46(s,2H,CH2),6.99(s,2H,NH2),8.02(s,1H,pyrimidin-5-yl-H),8.10(d,2H,Ar-H,J＝7.5Hz),8.32(d,2H,Ar-H,J＝8.2Hz)；
13C NMR(100MHz,DMSO-d6)(ppm):162.25,161.13,159.40,148.27,142.72,140.78,133.07,129.12,122.43,122.31,107.85,62.39,45.76,23.92,20.16；
ESI-MS m/z:510.1(M+H)+；
Example 49
The pure product is yellow solid, the yield is 78 percent, and the m.p.128-130 ℃;
elemental analysis/%: calculated values: c, 40.09; h, 3.17; n, 19.25; measured value: c, 40.32; h, 3.22; n,19.35.
1H NMR(400MHz,DMSO-d6)(ppm):2.36(s,3H,CH3),3.03(s,2H,CH2),4.54(s,2H,CH2),5.47(s,2H,CH2),7.03(s,2H,NH2),7.80(s,4H,Ar-H),8.04(s,1H,pyrimidin-5-yl-H)；
13C NMR(100MHz,DMSO-d6)(ppm):161.58,160.21,158.49,144.88,141.77,140.00,131.52,130.74,127.70,127.51,123.21,121.77,106.77,62.01,44.07,22.14,19.49；
ESI-MS m/z:510.2(M+H)+；
Example 50
The pure product is yellow solid, the yield is 78 percent, and the purity is m.p.119-121 ℃;
elemental analysis/%: calculated values: c, 40.94; h, 3.23; n, 16.85; measured value: c, 41.12; h, 3.45; n, 16.96.;
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),3.09(s,2H,CH2),4.57(s,2H,CH2),5.58(s,2H,CH2),7.24(s,2H,NH2),7.43(s,1H,Ar),7.57(s,3H,Ar),7.73(s,1H,pyrimidin-5-yl-H)；
ESI-MS m/z:499.2(M+H)+；
example 51
The pure product is yellow solid, the yield is 85 percent, and the purity is m.p.163-165 ℃;
elemental analysis/%: calculated values: c, 40.82; h, 3.02; n, 16.80; measured value: c, 40.88; h, 3.26; n, 19.90.;
1H NMR(400MHz,DMSO-d6)(ppm):2.53(s,3H,CH3),3.12(s,2H,CH2),4.52(s,2H,CH2),5.68(s,2H,CH2),7.26(s,1H,Ar-H),7.44(t,1H,Ar-H,J＝9.9Hz),7.95(d,1H,Ar-H,J＝6.8Hz),8.32(s,2H,NH2)；
ESI-MS m/z:501.3(M+H)+；
example 52
The pure product is yellow solid, the yield is 77 percent, and the m.p.170-180 ℃;
elemental analysis/%: calculated values: c, 43.74; h, 3.87; n, 17.00; measured value: c, 43.98; h, 3.99; n,17.32.
1H NMR(400MHz,DMSO-d6)(ppm):2.51(s,3H,CH3),3.06(s,2H,CH2),3.83(s,3H,OCH3),4.49(s,2H,CH2),5.55(s,2H,CH2),7.01(d,2H,Ar-H,J＝5.3Hz),7.11(s,2H,NH2),7.84(s,2H,Ar-H)；
ESI-MS m/z:495.3(M+H)+；
Example 53
The obtained pure product is yellow solid, the yield is 85 percent, and the m.p.158-160 ℃;
elemental analysis/%: calculated values: c, 42.34; h, 3.34; n, 17.43; measured value: c, 42.45; h, 3.52; n,17.65.
1H NMR(400MHz,DMSO-d6)(ppm):2.40(s,3H,CH3),3.07(s,2H,CH2),4.55(s,2H,CH2),5.50(s,2H,CH2),7.06(s,2H,NH2),7.30(s,2H,Ar-H),7.66(s,1H,Ar-H),7.81(s,2H,Ar-H)；
13C NMR(100MHz,DMSO-d6)(ppm):；
ESI-MS m/z:483.3(M+H)+；
Example 54
The pure product is yellow solid, the yield is 79 percent, and the m.p. is 169 to 171 ℃;
elemental analysis/%: calculated values: c, 42.34; h, 3.34; n, 17.43; measured value: c, 42.56; h, 3.54; n, 17.36.;
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),3.08(s,2H,CH2),4.53(s,2H,CH2),5.54(s,2H,CH2),7.03(s,2H,NH2),7.32(s,2H,Ar-H),7.95(s,2H,Ar-H)；
ESI-MS m/z:483.3(M-Cl)+；
example 55
The pure product is yellow solid, the yield is 88 percent, and the purity is m.p.195-197 ℃;
elemental analysis/%: calculated values: c, 40.94; h, 3.23; n, 16.85; measured value: c, 41.02; h, 3.42; n, 19.98.;
1H NMR(400MHz,DMSO-d6)(ppm):2.38(s,3H,CH3),3.06(s,2H,CH2),4.53(s,2H,CH2),5.48(s,2H,CH2),6.97(s,2H,NH2),7.55(s,2H,Ar-H),7.85(s,2H,Ar-H)；
13C NMR(100MHz,DMSO-d6)(ppm):164.57,162.68,160.90,142.01,138.02,130.92,128.75,128.09,109.16,63.35,46.94,25.33,21.07；
ESI-MS m/z:499.2(M+H)+；
example 56
The pure product is yellow solid, the yield is 76 percent, and the m.p.185-186 ℃;
elemental analysis/%: calculated values: c, 38.30; h, 2.84; n, 15.76; measured value: c, 38.52; h, 2.98; n, 15.86.;
1H NMR(400MHz,DMSO-d6)(ppm):2.43(s,3H,CH3),3.08(s,2H,CH2),4.56(s,2H,CH2),5.52(s,2H,CH2),7.08(s,2H,NH2),7.53(s,1H,Ar-H),7.76(s,2H,Ar-H)；
ESI-MS m/z:533.2(M-Cl)+；
example 57
The pure product is yellow solid, the yield is 81 percent, and the purity is m.p.172-177 ℃;
elemental analysis/%: calculated values: c, 40.09; h, 3.17; n, 19.25; measured value: c, 40.32; h, 3.22; n, 19.35;
1H NMR(400MHz,DMSO-d6)(ppm):2.36(s,3H,CH3),3.11(s,2H,CH2),4.60(s,2H,CH2),5.46(s,2H,CH2),7.08(s,2H,NH2),7.80(d,1H,Ar-H,J＝7.0Hz),8.28(d,1H,Ar-H,J＝6.6Hz),8.47(d,1H,Ar-H,J＝6.7Hz),8.57(s,1H,Ar-H)；
13C NMR(100MHz,DMSO-d6)(ppm):163.05,162.20,162.10,160.43,160.36,146.94,143.32,141.54,134.66,130.22,127.19,122.76,108.88,63.62,46.50,24.11,20.77；
ESI-MS m/z:510.3(M+H)+；
example 58
The pure product is yellow solid, the yield is 81 percent, and the purity is m.p.198-200 ℃;
elemental analysis/%: calculated values: c, 37.55; h, 2.78; n, 18.00; measured value: c, 37.66; h, 2.96; n, 18.21;
1H NMR(400MHz,DMSO-d6)(ppm):2.56(s,3H,CH3),3.12(s,2H,CH2),4.62(s,2H,CH2),5.50(s,2H,CH2),7.91(s,1H,Ar-H),8.04(d,1H,Ar-H,J＝7.4Hz),8.29(d,1H,Ar-H,J＝6.9Hz),8.37(s,1H,NH2),8.76(s,1H,NH2),9.29(s,1H,pyrimidin-5-yl-H)；
13C NMR(100MHz,DMSO-d6)(ppm):161.53,160.85,159.14,147.13,140.60,133.29,130.72,130.61,123.58,120.88,107.24,62.69,45.77,23.76,20.32；
ESI-MS m/z:544.2(M+H)+；.
example 59
The pure product is yellow solid, the yield is 86 percent, and the m.p.186-188 ℃;
elemental analysis/%: calculated values: c, 37.59; h, 2.97; n, 15.47; measured value: c, 37.66; h, 3.02; n, 15.65;
1H NMR(400MHz,DMSO-d6)(ppm):2.36(s,3H,CH3),3.06(s,2H,CH2),4.52(s,2H,CH2),5.49(s,2H,CH2),6.97(s,2H,NH2),7.69(s,2H,Ar-H),7.76(s,2H,Ar-H)；
13C NMR(100MHz,DMSO-d6)(ppm):162.60,160.57,158.86,140.27,130.03,129.18,126.30,125.31,107.00,61.41,45.53,23.60,20.04；
ESI-MS m/z:543.1(M+H)+；
example 60
The pure product is yellow solid, the yield is 75 percent, and the purity is m.p.168-169 ℃;
elemental analysis/%: calculated values: c, 37.59; h, 2.97; n, 15.47; measured value: c, 37.62; h, 3.02; n, 15.65.;
1H NMR(400MHz,DMSO-d6)(ppm):2.51(s,3H,CH3),3.09(s,2H,CH2),4.54(s,2H,CH2),5.51(s,2H,CH2),7.16(s,2H,NH2),7.48(s,1H,Ar-H),7.87(s,2H,Ar-H),8.02(s,1H,Ar-H)；
13C NMR(100MHz,DMSO-d6)(ppm):158.30,157.21,157.10,155.85,138.82,137.11,130.70,125.78,122.72,122.57,116.10,103.55,57.93,42.32,20.12,17.07；
ESI-MS m/z:543.2(M+H)+；
example 61
Preparation of Compound 61
Dissolving 1mmol of 2-methyl-4-amino-5-methyl azidopyrimidine and 1mmol of substituted thiazolium 1,3, 4-oxadiazole thioether propyne in 6mL of acetone solvent, respectively adding 0.01mmol of CuBr and 1mmol of triethylamine, stirring the reaction solution at 30-50 ℃ for 1h, and pouring the reaction solution into 50mL of water to separate out a large amount of solid. Filtration gave the title compound as a grey solid in 85% yield, mp: 229 ℃ at 230 ℃;
elemental analysis/%: calculated values: c, 43.26; h, 3.87; n, 33.63; measured value: c, 43.32; h, 3.98; n, 33.56;
1H NMR(400MHz,DMSO-d6)(ppm):2.30(s,3H,CH3),2.36(s,3H,CH3),4.54(s,2H,CH2),5.42(s,2H,CH2),6.93(s,2H,NH2),7.76(s,2H,NH2),8.10(s,1H,triazole-H)；
ESI-MS m/z:417.3(M+1)+；
compounds 62-64 were prepared analogously to Compound 61 and have the following structure identification data:
example 62
The pure product is gray solid, the yield is 86 percent, and the m.p. is 189-191 ℃;
elemental analysis/%: calculated values: c, 44.64; h, 4.21; n, 32.54; measured value: c, 44.68; h, 4.32; n, 32.65;
1H NMR(400MHz,DMSO-d6)(ppm):2.31(s,3H,CH3),2.40(s,3H,CH3),2.87(s,3H,CH3),4.54(s,2H,CH2),5.43(s,2H,CH2),6.95(s,2H,NH2),8.10(s,1H,NH),8.28(s,1H,triazole-H)；ESI-MS m/z:431.4(M+1)+；
example 63
The pure product is gray solid, the yield is 81 percent, and the m.p.201-202 ℃;
elemental analysis/%: calculated values: c, 38.29; h, 2.79; n, 29.77; measured value: c, 38.33; h, 2.98; n, 29.89;
1H NMR(400MHz,DMSO-d6)(ppm):2.32(s,3H,CH3),4.58(s,2H,CH2),5.47(s,2H,CH2),7.02(s,2H,NH2),8.12(s,1H,triazole-H),8.29(s,2H,NH2),；
ESI-MS m/z:471.3(M+1)+；
example 64
The pure product is gray solid, the yield is 79 percent, and the m.p.197-198 ℃;
elemental analysis/%: calculated values: c, 39.67; h, 3.12; n, 28.91; measured value: c, 39.86; h, 3.25; n, 28.98;
1H NMR(400MHz,DMSO-d6)(ppm):2.52(s,3H,CH3),2.92(s,3H,CH3),4.61(s,2H,CH2),5.63(s,2H,CH2),7.17(s,2H,NH2),8.16(s,1H,triazole-H),8.80(s,1H,NH),；
ESI-MS m/z:485.3(M+1)+；
example 65
Preparation of Compound 65
Dissolving 1mmol of 2-methyl-4-amino-5-methyl azidopyrimidine and 1mmol of iodo-substituted thiazolium 1,3, 4-oxadiazole thioether propyne in 5mL of trichloromethane, respectively adding 0.05mmol of CuI and 2mmol of triethylamine, stirring at 40-50 ℃ for reaction for 12h, adding water, stirring to separate out a solid, performing suction filtration, and drying to obtain a yellow solid, wherein the obtained pure product is a gray solid, the yield is 86%, and m.p.158-160 ℃;
elemental analysis/%: calculated values: c, 43.26; h, 3.87; n, 33.63; measured value: c, 43.36; h, 3.96; n, 33.56;
1H NMR(400MHz,DMSO-d6)(ppm):2.41(s,6H,2CH3),4.51(s,2H,CH2),5.62(s,2H,CH2),7.37(s,2H,NH2),7.87(s,2H,NH2)；
ESI-MS m/z:543.3(M+1)+；
compounds 66-68 were prepared analogously to Compound 65 and have the following structure identification data:
example 66
The pure product is yellow solid, the yield is 87 percent, and the m.p.169-170 ℃;
elemental analysis/%: calculated values: c, 34.54; h, 3.08; n, 25.17; measured value: c, performing phase inversion; h,; n;
1H NMR(400MHz,DMSO-d6)(ppm):2.42(s,6H,2CH3),2.86(s,3H,CH3),4.50(s,2H,CH2),5.47(s,2H,CH2),7.23(s,2H,NH2),8.33(s,1H,NH)；
ESI-MS m/z:556.2(M+1)+；
example 67
The pure product is gray solid, the yield is 88 percent, and the purity is m.p.192-194 ℃;
elemental analysis/%: calculated values: c, 30.21; h, 2.03; n, 23.49; measured value: c, 30.32; h, 2.32; n, 23.56;
1H NMR(400MHz,DMSO-d6)(ppm):2.50(s,3H,CH3),4.54(s,2H,CH2),5.56(s,2H,CH2),7.19(s,2H,NH2),8.29(s,2H,NH2),；
ESI-MS m/z:596.2(M+1)+；
example 68
The pure product is gray solid, the yield is 80 percent, and the m.p.177-178 ℃;
elemental analysis/%: calculated values: c, 31.48; h, 2.31; n, 22.95; measured value: c, 31.65; h, 2.55; n, 23.12;
1H NMR(400MHz,DMSO-d6)(ppm):2.45(s,3H,CH3),2.91(s,3H,CH3),4.53(s,2H,CH2),5.47(s,2H,CH2),7.01(s,2H,NH2),8.80(s,1H,NH),
ESI-MS m/z:611.2(M+1)+；
example 69
Preparation of Compound 69
Dissolving 1mmol of 2-methyl-4-amino-5-methyl azidopyrimidine and 1mmol of substituted thiazolium 1- (amino) -3, 4-triazole thioether propyne in 5mL of anhydrous tetrahydrofuran, respectively adding 0.05mmol of CuI and 0.5mmol of triethylamine, stirring and reacting for 12h at the temperature of 40-50 ℃, adding water, stirring to separate out a solid, performing suction filtration, drying to obtain a yellow solid, wherein the yield is 86%, and the mp: 219-220 ℃;
elemental analysis/%: calculated values: c, 41.85; h, 4.21; n, 39.04; measured value: c, 41.98; h, 4.35; n, 39.36;
1H NMR(400MHz,DMSO-d6)(ppm):2.31(s,3H,CH3),2.37(s,3H,CH3),4.46(s,2H,CH2),5.42(s,2H,CH2),5.99(s,2H,NH2),6.96(s,2H,NH2),7.23(s,2H,NH2),8.10(s,1H,triazole-H),8.10(s,1H,pyrimidine-H)；
ESI-MS m/z:431.4(M+1)+；
compounds 70-72 were prepared analogously to Compound 69 and have the following structure identification data:
example 70
The pure product is yellow solid, the yield is 76 percent, and the purity is m.p.188-189 ℃;
elemental analysis/%: calculated values: c, 43.23; h, 4.53; n, 37.81; measured value: c, 43.25; h, 4.65; n, 37.96;
1H NMR(400MHz,DMSO-d6)(ppm):2.31(s,3H,CH3),2.41(s,3H,CH3),2.86(s,3H,CH3),4.53(s,2H,CH2),5.46(s,2H,CH2),6.95(s,2H,NH2),7.05(s,2H,NH2),8.16(s,1H,NH),8.24(s,1H,triazole-H)
ESI-MS m/z:445.2(M+1)+；
example 71
The pure product is brown solid, the yield is 77 percent, and the m.p. is 169 to 171 ℃;
elemental analysis/%: calculated values: c, 37.19; h, 3.12; n, 34.69; measured value: c, 37.23; h, 3.25; n,34.87.
1H NMR(400MHz,DMSO-d6)(ppm):2.32(s,3H,CH3),4.52(s,2H,CH2),5.46(s,2H,CH2),6.02(s,2H,NH2),7.01(s,2H,NH2),7.82(s,2H,NH2),8.13(s,1H,triazole-H)；
ESI-MS m/z:485.4(M+1)+；
Example 72
The pure product is yellow solid, the yield is 75 percent, and the purity is m.p.156-157 ℃;
elemental analysis/%: calculated values: c, 38.55; h, 3.44; n, 33.72; measured value: c, 38.63; h, 3.56; n, 33.86;
1H NMR(400MHz,DMSO-d6)(ppm):2.31(s,3H,CH3),2.88(s,3H,CH3),4.48(s,2H,CH2),5.45(s,2H,CH2),6.01(s,2H,NH2),6.96(s,2H,NH2),8.10(s,1H,triazole-H),8.32(s,1H,NH)；ESI-MS m/z:499.4(M+1)+；
pharmacological activity screening experiment
Example 73
Experiment of agricultural bacterial Activity
Test materials: bacterial brown spot and white leaf spot of rice
The test method comprises the following steps: the method for determining antibacterial effect of compound mainly adopts a bacteria plate counting method, and comprises the specific steps of firstly diluting 10 mu L of treated bacteria liquid into 90 mu L of physiological saline, and diluting the bacteria liquid to 10 percent by using a 10-fold dilution method-7cfu/ml; and then transferred from 10 using a pipette-1cfu/mL、10-2cfu/mL、10-3cfu/mL、10-4cfu/mL、10-5cfu/mL、10-6cfu/mL、10-7Selecting bacterial liquid 10 μ L drop plates with 3 concentrations (wherein rice bacterial brown streak disease Aaa is dropped on LB plate, and rice bacterial blight bacterial Xoo is dropped on NA) in cfu/mL solution according to conditions, and repeating each treatment for 3 times; and finally, after each plate is dried, culturing each plate for 24 hours at the temperature of 3 ℃, selecting the plate with the colony number of 10-200 for counting, and calculating the bacterial amount in the original bacterial liquid to obtain the bactericidal activity of the compound.
Calculating the formula:
the total viable count per ml of reaction solution is the average number of colonies at the same dilution x10
Bacteriostatic ratio (number of bacteria treated without compound-number of bacteria treated with compound or positive drug)/number of bacteria treated without compound × 100%
TABLE 1 preliminary screening Activity of some of the compounds (test concentration 500ppm)
The compound of the general formula I has excellent bactericidal activity, can be used for preventing and treating rice bacterial brown spot pathogen and rice bacterial leaf blight pathogen, and the prevention and treatment effect of part of the compound on bacteria is equivalent to or better than that of a contrast commercial bactericide.
Example 74
Test of blue algae inhibitory Activity
Test materials: blue algae with model number of PCC6803
The test method comprises the following steps: adding blue algae in logarithmic growth phase into fresh culture solution at an inoculum size of 1%, culturing for 4-7 days, measuring absorbance at X680 mn with ultraviolet spectrophotometer, and diluting with culture solution to obtain algae cell number of about 1X106The absorbance of PCC6803 was 0.015 per mL, i.e. after dilution. mu.L of diluted algae solution was added to each well of a 96-well plate, followed by addition of L. mu.L of a concentration of compound (compound in DMSO), and mixing, in triplicate for each compound. Two controls were made, one with 200. mu.L algal solution alone, and the other with 200. mu.L algal solution and 10. mu.L DMSO. Sealing the 96-well plate, culturing in an artificial climate box, shaking on a shaking table for 30min every day, reading the light absorption value of each well at the wavelength of 680nm on a BIOTECK multifunctional microplate reader every 24 hours, sealing the 96-well plate after reading each time, and continuously culturing in the incubator.
The calculation formula of the inhibition rate is as follows:
growth inhibition rate (day n of OD680 control-day n of OD680 medium) - (day n of OD680 experimental group-day n of OD680 drug group)/(day n of OD680 control-day n of OD680 medium) 100%
Day n of the OD680 control group: 200 mu.L of algae solution and absorbance value of 1 mu L of LDMSO on the nth day
OD680 medium day n: absorbance on day n of 200 μ L BGll
OD680 experimental group day n: light absorption value of 200. mu.L algae solution and L. mu.L compound on day n
Day n of OD680 drug group: absorbance on day n of 200. mu.L BG11 and 1. mu.L Compound
TABLE 2 Primary Sieve Activity of part of the Compounds (test concentration 100ppm)
Compound numbering PCC6803 Compound numbering PCC6803 Compound numbering PCC6803
1 100 23 96 51 100
2 100 24 100 52 100
3 100 25 100 53 100
4 100 26 100 54 100
5 100 27 100 55 96
6 100 28 100 56 97
7 95 29 100 57 100
8 100 30 100 58 100
9 100 31 100 59 99
10 99 32 99 60 99
11 99 33 100 61 100
12 100 34 100 62 100
13 99 35 100 63 100
14 97 36 100 64 100
15 100 37 100 65 100
16 100 38 100 66 100
17 100 39 100 67 98
18 100 40 99 68 99
19 100 47 100 69 97
20 100 48 99 70 99
21 100 49 100 71 94
22 99 50 100 72 97
CuSO4 100
As shown in Table 2, the compound of the general formula I has excellent blue algae inhibiting activity, and the prevention and treatment effect of most compounds on blue algae can reach 94-100%, which is equivalent to that of a control medicament. Therefore, the compounds have great potential and application prospect in the aspect of controlling water bloom outbreak.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
While embodiments of the invention have been shown and described, it will be understood by those of ordinary skill in the art that: various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.

Claims (11)

1. A compound, which is a compound shown in formula I or an enantiomer, a diastereomer, a racemate, a pharmaceutically acceptable salt, a crystal hydrate or a solvate of the compound shown in formula I,
wherein,
R1is hydrogen or iodine;
x is O, S or NH;
y is carbonyl, sulfuryl or an optionally substituted aromatic heterocyclic group;
z is methyl, optionally substituted aromatic heterocyclic group, optionally substituted alkyl or optionally substituted phenyl;
n is 1,2, 3.
2. The compound of claim 1, wherein Y is a carbonyl group, a sulfone group, a,Or
3. A compound according to claim 1, wherein Z is methyl, optionally substituted phenyl,a furyl group, a thienyl group,
wherein,
R2is methyl or trifluoromethyl;
R3is amino or methylamino.
4. The compound of claim 1, wherein Z is methyl, phenyl substituted with 1-2 nitro groups, phenyl substituted with 1-3 halogen groups, phenyl substituted with 1-3 methyl groups, phenyl substituted with methoxy groups,A furyl group, a thienyl group,
wherein,
R2is methyl or trifluoromethyl;
R3is amino or methylAn amino group;
optionally, the halogen is fluorine, chlorine, bromine or iodine.
5. The compound of claim 1, wherein Z is methyl, phenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 3, 5-dinitrophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-chlorophenyl, 3-chlorophenyl, 2, 4-dichlorophenyl, 4-fluorophenyl, 3-fluorophenyl, 2, 4-difluorophenyl, 3-bromophenyl, 4-methylphenyl, 3-methylphenyl, 2, 4-dimethylphenyl, 2,4, 6-trimethylphenyl, 3-nitro-4-chlorophenyl, 3-nitrophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, or a mixture thereof, 2-chloro-4-nitrophenyl,A furyl group, a thienyl group,
wherein,
R2is methyl or trifluoromethyl;
R3is amino or methylamino.
6. The compound according to claim 1, wherein the compound is the following compound or an enantiomer, diastereomer, racemate, pharmaceutically acceptable salt, crystalline hydrate or solvate of the following compound:
7. a process for preparing a compound according to any one of claims 1 to 6, comprising: contacting a compound of formula II with a compound of formula III to obtain a compound of formula I,
wherein X, Y, Z, n, R1、R2、R3Is as defined in any one of claims 1 to 6.
8. The method for preparing the compound according to claim 7, wherein the contacting is performed by dissolving the compound of formula II and the compound of formula III in a first organic solvent, adding a catalyst and an organic base, and stirring,
optionally, the molar ratio of the compound shown in the formula II to the compound shown in the formula III, the catalyst and the organic base is 1:1-1.5: 0.01-0.15: 0.5 to 2;
optionally, the first organic solvent is at least one of acetonitrile, 1, 2-dichloroethane, acetone, tert-butanol, water, toluene, benzene, xylene, ethyl acetate, N-hexane, dichloromethane, chloroform, tetrahydrofuran, dimethyl sulfoxide, or N, N-dimethylformamide;
optionally, the catalyst is CuSO4·5H2O, sodium ascorbate, CuBr (PPh)3)3CuBr, CuI, or Cu (OAc)2At least one of;
optionally, the organic base is at least one of triethylamine, diethylamine, DMAP, diisopropylethylamine, N-methylmorpholine, pyridine, or piperidine.
9. A pesticide characterized by comprising a compound as defined in any one of claims 1 to 6.
10. A method of treating or preventing a plant disease, wherein a compound according to any one of claims 1 to 6, or a pesticide according to claim 9, is applied to the plant, optionally wherein the plant disease is caused by at least one of:
rice bacterial brown spot pathogen, rice white leaf blight pathogen;
optionally, the plant is rice.
11. A method for removing blue-green algae, characterized in that the compound according to any one of claims 1 to 6 or the pesticide according to claim 9 is applied to blue-green algae.
CN201510672520.1A 2015-10-16 2015-10-16 Compound and preparation method and application thereof Active CN106588887B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510672520.1A CN106588887B (en) 2015-10-16 2015-10-16 Compound and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510672520.1A CN106588887B (en) 2015-10-16 2015-10-16 Compound and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN106588887A true CN106588887A (en) 2017-04-26
CN106588887B CN106588887B (en) 2020-09-01

Family

ID=58553756

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510672520.1A Active CN106588887B (en) 2015-10-16 2015-10-16 Compound and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN106588887B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108976214A (en) * 2017-06-05 2018-12-11 华中师范大学 Pyruvate dehydrogenase system inhibitor and its preparation method and application

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102993185A (en) * 2011-09-13 2013-03-27 华中师范大学 Preparation method and bactericidal activity of 2-methyl-4-amino-5-(substituted-1H-1,2,3-triazolyl) methylpyrimidine derivative
EP2626356A1 (en) * 2012-02-08 2013-08-14 Rheinische Friedrich-Wilhelms-Universität Bonn Thiamine analogues and their use as antibiotics
CN104892581A (en) * 2014-03-07 2015-09-09 华中师范大学 2-methyl-4-amino-5-(substituted-1,2,3-triazolyl)methylpyridine derivatives having bactericidal activity, and preparation method and application thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102993185A (en) * 2011-09-13 2013-03-27 华中师范大学 Preparation method and bactericidal activity of 2-methyl-4-amino-5-(substituted-1H-1,2,3-triazolyl) methylpyrimidine derivative
EP2626356A1 (en) * 2012-02-08 2013-08-14 Rheinische Friedrich-Wilhelms-Universität Bonn Thiamine analogues and their use as antibiotics
CN104892581A (en) * 2014-03-07 2015-09-09 华中师范大学 2-methyl-4-amino-5-(substituted-1,2,3-triazolyl)methylpyridine derivatives having bactericidal activity, and preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KARL M. ERIXON等: "Inhibition of pyruvate decarboxylase from Z. mobilis by novel analogues of thiamine pyrophosphate: investigating pyrophosphate mimics", 《CHEMICAL COMMUNICATIONS (CAMBRIDGE, UNITED KINGDOM)》 *
LUENSE, CHRISTINA E.等: "Novel TPP-riboswitch activators bypass metabolic enzyme dependency", 《 FRONTIERS IN CHEMISTRY (LAUSANNE, SWITZERLAND)》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108976214A (en) * 2017-06-05 2018-12-11 华中师范大学 Pyruvate dehydrogenase system inhibitor and its preparation method and application
CN108976214B (en) * 2017-06-05 2020-09-29 华中师范大学 Pyruvic acid dehydrogenase inhibitor and preparation method and application thereof

Also Published As

Publication number Publication date
CN106588887B (en) 2020-09-01

Similar Documents

Publication Publication Date Title
CN108997253B (en) Mandelic acid derivatives containing 1,3, 4-oxadiazole thioether and application thereof
CN113527221B (en) Dekkolii derivative, application thereof and bactericide for resisting plant mycosis
JPS6233171A (en) 1-heteroaryl-4-aryl-pyrazole derivative, manufacture and use
WO1987003591A1 (en) Novel imidazole derivatives, bactericides containing them, and process for their preparation
CN102746282B (en) N-5-substituted phenyl-2-furoyl compounds, preparation method and application thereof
US4792565A (en) Pyrazolecarbonylamine derivatives and agricultural and horticultural fungicides containing said compounds
SU1050564A3 (en) Process for preparing derivatives of nitrothiphene
WO2013037289A1 (en) Preparation of derivative of 2-methyl-4-amino-5-（substituted-1h-1,2,3-triazol）methyl pyrimidine and microbicidal activity thereof
CN106588887B (en) Compound and preparation method and application thereof
CN108976214B (en) Pyruvic acid dehydrogenase inhibitor and preparation method and application thereof
JPH0559024A (en) Isothiazole carboxylic acid derivative and pyricularia oryzae control agent containing the same as active ingredient
CN108383790B (en) Amide compound containing pyrazole ring, preparation method and application thereof
CN102617482B (en) Containing trifluoromethyl pyrimidine ammoniate, preparation method and the purposes as sterilant
CN109666004B (en) Trifluoromethyl-containing pyrazinamide compounds, preparation method and application thereof, and bactericide
CN111499587A (en) Methoxy acrylate compound containing 1,2, 4-triazole Schiff base and preparation method and application thereof
CN110357857A (en) Pyrazinamide class compound and its preparation method and application and fungicide
CN113896722B (en) Benzamide compound containing thiadiazole group and preparation method and application thereof
JPS63253085A (en) Harmful organism control agent based on 1, 10-phenanthrolines
CN111285815A (en) Pyrazinamide compound and application thereof
CN111285801B (en) Pyridine amide compound and application
CN108570009A (en) 3- halogens diaryl-amine base pyrazol acid amide compounds and its application in pesticide
CN109096209B (en) Pyrazinamide compounds, preparation method and application thereof, and bactericide
CN116178359A (en) Heterocyclic substitution-based disulfide derivative, preparation method and application thereof
US4315846A (en) Metal salt of N-substituted alkylenebisdithiocarbamic acid
KR100501146B1 (en) Triazole derivatives for antifungal composition of agriculture, method of preparing same and antifungal composition comprising same for agriculture

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
EE01 Entry into force of recordation of patent licensing contract

Application publication date: 20170426

Assignee: Hubei Juhui New Material Industry Technology Research Institute Co.,Ltd.

Assignor: CENTRAL CHINA NORMAL University

Contract record no.: X2022420000147

Denomination of invention: Compound and its preparation method and application

Granted publication date: 20200901

License type: Common License

Record date: 20221228

EE01 Entry into force of recordation of patent licensing contract
EE01 Entry into force of recordation of patent licensing contract

Application publication date: 20170426

Assignee: Wuhan Nanwang Environmental Protection Technology Research Co.,Ltd.

Assignor: CENTRAL CHINA NORMAL University

Contract record no.: X2023980053268

Denomination of invention: Compounds and their preparation methods and applications

Granted publication date: 20200901

License type: Common License

Record date: 20231220

EE01 Entry into force of recordation of patent licensing contract